-
Parasites & Vectors Jan 2021Toxoplasma gondii is a protozoan parasite with a complex life cycle and a cosmopolitan host range. The asexual part of its life cycle can be perpetually sustained in a... (Review)
Review
Toxoplasma gondii is a protozoan parasite with a complex life cycle and a cosmopolitan host range. The asexual part of its life cycle can be perpetually sustained in a variety of intermediate hosts through a combination of carnivory and vertical transmission. However, T. gondii produces gametes only in felids after the predation of infected intermediate hosts. The parasite changes the behavior of its intermediate hosts by reducing their innate fear to cat odors and thereby plausibly increasing the probability that the definitive host will devour the infected host. Here, we provide a short description of such parasitic behavioral manipulation in laboratory rodents infected with T. gondii, along with a bird's eye view of underpinning biological changes in the host. We also summarize critical gaps and opportunities for future research in this exciting research area with broad implications in the transdisciplinary study of host-parasite relationships.
Topics: Animals; Behavior, Animal; Cats; Fear; Host-Parasite Interactions; Humans; Life Cycle Stages; Odorants; Rodentia; Toxoplasma; Toxoplasmosis, Animal
PubMed: 33494777
DOI: 10.1186/s13071-020-04528-x -
Cell Host & Microbe Nov 2020Apicomplexan parasites cause major human disease and food insecurity. They owe their considerable success to highly specialized cell compartments and structures. These...
Apicomplexan parasites cause major human disease and food insecurity. They owe their considerable success to highly specialized cell compartments and structures. These adaptations drive their recognition, nondestructive penetration, and elaborate reengineering of the host's cells to promote their growth, dissemination, and the countering of host defenses. The evolution of unique apicomplexan cellular compartments is concomitant with vast proteomic novelty. Consequently, half of apicomplexan proteins are unique and uncharacterized. Here, we determine the steady-state subcellular location of thousands of proteins simultaneously within the globally prevalent apicomplexan parasite Toxoplasma gondii. This provides unprecedented comprehensive molecular definition of these unicellular eukaryotes and their specialized compartments, and these data reveal the spatial organizations of protein expression and function, adaptation to hosts, and the underlying evolutionary trajectories of these pathogens.
Topics: Apicomplexa; Biological Evolution; Epitopes; Host-Pathogen Interactions; Humans; Proteome; Proteomics; Protozoan Proteins; Toxoplasma
PubMed: 33053376
DOI: 10.1016/j.chom.2020.09.011 -
Cell Sep 2016Apicomplexan parasites are leading causes of human and livestock diseases such as malaria and toxoplasmosis, yet most of their genes remain uncharacterized. Here, we...
Apicomplexan parasites are leading causes of human and livestock diseases such as malaria and toxoplasmosis, yet most of their genes remain uncharacterized. Here, we present the first genome-wide genetic screen of an apicomplexan. We adapted CRISPR/Cas9 to assess the contribution of each gene from the parasite Toxoplasma gondii during infection of human fibroblasts. Our analysis defines ∼200 previously uncharacterized, fitness-conferring genes unique to the phylum, from which 16 were investigated, revealing essential functions during infection of human cells. Secondary screens identify as an invasion factor the claudin-like apicomplexan microneme protein (CLAMP), which resembles mammalian tight-junction proteins and localizes to secretory organelles, making it critical to the initiation of infection. CLAMP is present throughout sequenced apicomplexan genomes and is essential during the asexual stages of the malaria parasite Plasmodium falciparum. These results provide broad-based functional information on T. gondii genes and will facilitate future approaches to expand the horizon of antiparasitic interventions.
Topics: Apicomplexa; Cells, Cultured; Claudins; Clustered Regularly Interspaced Short Palindromic Repeats; Fibroblasts; Genome, Protozoan; Genome-Wide Association Study; Host-Parasite Interactions; Humans; Malaria, Falciparum; Plasmodium falciparum; Protozoan Proteins; Toxoplasma; Toxoplasmosis
PubMed: 27594426
DOI: 10.1016/j.cell.2016.08.019 -
Cell Host & Microbe Apr 2023Cryptosporidium is a leading cause of diarrheal disease in children and an important contributor to early childhood mortality. The parasite invades and extensively...
Cryptosporidium is a leading cause of diarrheal disease in children and an important contributor to early childhood mortality. The parasite invades and extensively remodels intestinal epithelial cells, building an elaborate interface structure. How this occurs at the molecular level and the contributing parasite factors are largely unknown. Here, we generated a whole-cell spatial proteome of the Cryptosporidium sporozoite and used genetic and cell biological experimentation to discover the Cryptosporidium-secreted effector proteome. These findings reveal multiple organelles, including an original secretory organelle, and generate numerous compartment markers by tagging native gene loci. We show that secreted proteins are delivered to the parasite-host interface, where they assemble into different structures including a ring that anchors the parasite into its unique epicellular niche. Cryptosporidium thus uses a complex set of secretion systems during and following invasion that act in concert to subjugate its host cell.
Topics: Child, Preschool; Child; Humans; Cryptosporidium; Proteome; Cryptosporidiosis; Organelles; Cryptosporidium parvum; Protozoan Proteins; Host-Parasite Interactions
PubMed: 36958336
DOI: 10.1016/j.chom.2023.03.001 -
The Journal of Eukaryotic Microbiology Nov 2022Toxoplasma gondii belongs to the phylum Apicomplexa and is an important cause of congenital disease and infection in immunocompromised patients. T. gondii shares... (Review)
Review
Toxoplasma gondii belongs to the phylum Apicomplexa and is an important cause of congenital disease and infection in immunocompromised patients. T. gondii shares several characteristics with plants including a nonphotosynthetic plastid termed apicoplast and a multivesicular organelle that was named the plant-like vacuole (PLV) or vacuolar compartment (VAC). The name plant-like vacuole was selected based on its resemblance in composition and function to plant vacuoles. The name VAC represents its general vacuolar characteristics. We will refer to the organelle as PLVAC in this review. New findings in recent years have revealed that the PLVAC represents the lysosomal compartment of T. gondii which has adapted peculiarities to fulfill specific Toxoplasma needs. In this review, we discuss the composition and functions of the PLVAC highlighting its roles in ion storage and homeostasis, endocytosis, exocytosis, and autophagy.
Topics: Humans; Toxoplasma; Vacuoles; Protozoan Proteins; Apicoplasts; Plants
PubMed: 36218001
DOI: 10.1111/jeu.12951 -
Trends in Parasitology Oct 2023Meiosis is sexual cell division, a process in eukaryotes whereby haploid gametes are produced. Compared to canonical model eukaryotes, meiosis in apicomplexan parasites... (Review)
Review
Meiosis is sexual cell division, a process in eukaryotes whereby haploid gametes are produced. Compared to canonical model eukaryotes, meiosis in apicomplexan parasites appears to diverge from the process with respect to the molecular mechanisms involved; the biology of Plasmodium meiosis, and its regulation by means of post-translational modification, are largely unexplored. Here, we discuss the impact of technological advances in cell biology, evolutionary bioinformatics, and genome-wide functional studies on our understanding of meiosis in the Apicomplexa. These parasites, including Plasmodium falciparum, Toxoplasma gondii, and Eimeria spp., have significant socioeconomic impact on human and animal health. Understanding this key stage during the parasite's life cycle may well reveal attractive targets for therapeutic intervention.
Topics: Animals; Humans; Plasmodium; Eukaryota; Plasmodium falciparum; Meiosis; Toxoplasma
PubMed: 37541799
DOI: 10.1016/j.pt.2023.07.002 -
Parasites & Vectors Jan 2022Apicomplexans are important pathogens that cause severe infections in humans and animals. The biology and pathogeneses of these parasites have shown that proteins are... (Review)
Review
Apicomplexans are important pathogens that cause severe infections in humans and animals. The biology and pathogeneses of these parasites have shown that proteins are intrinsically modulated during developmental transitions, physiological processes and disease progression. Also, proteins are integral components of parasite structural elements and organelles. Among apicomplexan parasites, Eimeria species are an important disease aetiology for economically important animals wherein identification and characterisation of proteins have been long-winded. Nonetheless, this review seeks to give a comprehensive overview of constitutively expressed Eimeria proteins. These molecules are discussed across developmental stages, organelles and sub-cellular components vis-à-vis their biological functions. In addition, hindsight and suggestions are offered with intention to summarise the existing trend of eimerian protein characterisation and to provide a baseline for future studies.
Topics: Animals; Antigens, Protozoan; Apicomplexa; Bodily Secretions; Chickens; Coccidiosis; Eimeria; Eimeria tenella; Genes, Protozoan; Host-Parasite Interactions; Humans; Membrane Proteins; Merozoites; Oocysts; Organelles; Peptide Hydrolases; Poultry Diseases; Protein Transport; Sporozoites
PubMed: 35073987
DOI: 10.1186/s13071-022-05159-0 -
MBio Feb 2019Alternative splicing is a widespread, essential, and complex component of gene regulation. Apicomplexan parasites have long been recognized to produce alternatively... (Review)
Review
Alternative splicing is a widespread, essential, and complex component of gene regulation. Apicomplexan parasites have long been recognized to produce alternatively spliced transcripts for some genes and can produce multiple protein products that are essential for parasite growth. Recent approaches are now providing more wide-ranging surveys of the extent of alternative splicing; some indicate that alternative splicing is less widespread than in other model eukaryotes, whereas others suggest levels comparable to those of previously studied groups. In many cases, apicomplexan alternative splicing events appear not to generate multiple alternative proteins but instead produce aberrant or noncoding transcripts. Nonetheless, appropriate regulation of alternative splicing is clearly essential in and parasites, suggesting a biological role for at least some of the alternative splicing observed. Several studies have now disrupted conserved regulators of alternative splicing and demonstrated lethal effects in apicomplexans. This minireview discusses methods to accurately determine the extent of alternative splicing in Apicomplexa and discuss potential biological roles for this conserved process in a phylum of parasites with compact genomes.
Topics: Alternative Splicing; Animals; Apicomplexa; Gene Expression Regulation; Parasites
PubMed: 30782661
DOI: 10.1128/mBio.02866-18 -
International Journal For Parasitology May 2021Toxoplasma gondii is an obligatory intracellular pathogen that causes life threatening illness in immunodeficient individuals, miscarriage in pregnant woman, and... (Review)
Review
Toxoplasma gondii is an obligatory intracellular pathogen that causes life threatening illness in immunodeficient individuals, miscarriage in pregnant woman, and blindness in newborn children. Similar to any other eukaryotic cell, protein kinases play critical and essential roles in the Toxoplasma life cycle. Accordingly, many studies have focused on identifying and defining the mechanism of function of these signalling proteins with a long-term goal to develop anti-Toxoplasma therapeutics. In this review, we briefly discuss classification and key components of the catalytic domain which are critical for functioning of kinases, with a focus on domains, families, and groups of kinases within Toxoplasma. More importantly, this article provides a comprehensive, current overview of research on kinase groups in Toxoplasma including the established eukaryotic AGC, CAMK, CK1, CMGC, STE, TKL families and the apicomplexan-specific FIKK, ROPK and WNG family of kinases. This work provides an overview and discusses current knowledge on Toxoplasma kinases including their localization, function, signalling network and role in acute and chronic pathogenesis, with a view towards the future in probing kinases as viable drug targets.
Topics: Animals; Female; Humans; Infant, Newborn; Life Cycle Stages; Protein Kinases; Protozoan Proteins; Toxoplasma
PubMed: 33581139
DOI: 10.1016/j.ijpara.2020.11.006 -
Frontiers in Cellular and Infection... 2020Perforins are secreted proteins of eukaryotes, which possess a membrane attack complex/perforin (MACPF) domain enabling them to form pores in the membranes of target... (Review)
Review
Perforins are secreted proteins of eukaryotes, which possess a membrane attack complex/perforin (MACPF) domain enabling them to form pores in the membranes of target cells. In higher eukaryotes, they are assigned to immune defense mechanisms required to kill invading microbes or infected cells. Perforin-like proteins (PLPs) are also found in apicomplexan parasites. Here they play diverse roles during lifecycle progression of the intracellularly replicating protozoans. The apicomplexan PLPs are best studied in and , the causative agents of malaria and toxoplasmosis, respectively. The PLPs are expressed in the different lifecycle stages of the pathogens and can target and lyse a variety of cell membranes of the invertebrate and mammalian hosts. The PLPs thereby either function in host cell destruction during exit or in overcoming epithelial barriers during tissue passage. In this review, we summarize the various PLPs known for apicomplexan parasites and highlight their roles in and lifecycle progression.
Topics: Animals; Parasites; Perforin; Protozoan Proteins; Toxoplasma; Toxoplasmosis
PubMed: 33042876
DOI: 10.3389/fcimb.2020.578883